Using Epigenetics to Aid in the Diagnosis and Prevention of Autism Spectrum Disorders

According to the National Institutes of Health (NIH) autism spectrum disorders (ASD) are a range of complex neurodevelopmental disorders that can be characterized by social impairments, communication difficulties, as well as repetitive, stereotypical types of behavior, such as obsessive compulsive disorder (OCD). Classical Autism is the most severe form and Asperger's syndrome is the mildest form of ASD. It is estimated that 1 in every 88 children at the age of 8 will be diagnosed with an ASD, according to the Centers for Disease Control and Prevention. Males are 4 times more likely to be diagnosed with ASD than females.

It is currently unknown what exactly causes ASD, but scientists believe the environment as well as genetics may play a role. A number of genes have been associated with autism as well as irregularities within different sections of the brain. This suggests that there may be specific gene mutations that cause these brain abnormalities. Studies involving the role of epigenetics in ASD are still preliminary and much more work needs to be completed before any major conclusions can be drawn.

Epigenetics describes the molecular factors that form complexes at regulatory regions of DNA to influence genetic activity without changing the primary DNA sequence. DNA methylation is the most widely studied and widely understood epigenetic marker. Environmental factors are known to influence the occurrence of DNA methylation. As identified through previous genetic screens, genes that play a role in epigenetic pathways are associated with a large proportion of the genes associated with ASD. In addition, studies have shown that there is a good amount of evidence to support that the in utero early life environment may play a role in the development of ASD.

A recent review published in Frontiers in Neurology describes all the studies involving the epigenetic mark of DNA methylation on autism. They describe how research suggests that there are 5 genes which were epigenetically dysregulated in autism. These include the oxytocin receptor (OXTR), glutamate decarboxylase 1 (GAD1), engrailed-2 (EN2) reelin (RELN) and Methyl CpG binding protein 2 (MECP2). When looking into genome-wide epigenetic studies, the authors could identify 4 other genes not previously associated with autism. These include theoprolinerichtransmembraneprotein1 (PRRT1), zinc finger protein 57 (ZFP57), tetraspanin32 (TSPAN32) and the olfactory receptor gene (OR2L13). The authors found it particularly interesting that olfactory receptor gene OR2L13 was involved due to its role in the sense of smell. It is known that those with ASD tend to experience a lower sensory threshold where senses, such as smell, work overtime.

While this thorough review of the research surrounding epigenetics and autism helps to look at the "bigger picture" of how genes play a role in the development of autism, there is much more work to be done. It is predicted that future research will lead to the development of tests at birth, which may be able to predict the likelihood of a child developing autism and therefore; better informed treatments which will alleviate some of the symptoms of some of the most distressing cases of autism.

Sources: NIH, CDC, Frontiers in Neurology, EpiBeat